Fecal Microbiota Transplantation for Kidney Cancer

(PERFORM Trial)

Overseen By Ricardo Fernandes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: Antibiotics, Immunosuppressants, Steroids

Disqualifiers: Pregnancy, Immunodeficiency, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or antibiotics before the trial. It's best to discuss your specific medications with the trial team.

Is fecal microbiota transplantation (FMT) safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild and related to delivery methods. However, long-term side effects are not well-established, and serious adverse events have been linked to inadequate screening for multi-drug resistant organisms in some stool banks. ^{1 2 3 4 5}

How is fecal microbiota transplantation different from other treatments for kidney cancer?

Fecal microbiota transplantation (FMT) is unique because it involves transferring healthy gut bacteria from a donor to a patient to restore the balance of microorganisms in the gut, which may influence the body's immune response and metabolism. Unlike traditional cancer treatments like chemotherapy or radiation, FMT focuses on altering the gut microbiome to potentially impact cancer and its complications. ^{6 7 8 9 10}

What is the purpose of this trial?

Cancer immunotherapy has been largely adopted in oncology patient management in the last decade. The deep and long responses to immunotherapy have accelerated the approval of these drugs across multiple disease sites. However, these agents can also be toxic to patients, meaning, the patient will have to discontinue treatment and outcomes could be negatively affected. Recently, a combination of two immunotherapy drugs, ipilimumab and nivolumab (ipi/nivo), has been approved for the treatment of intermediate and poor-risk renal cell carcinoma (RCC) patients. This powerful combination provides survival benefit, however, it can also be highly toxic leading to discontinuation of this treatment. There has been some evidence that these otherwise toxic drugs can be better tolerated by altering the composition of the patients gut bacteria to create a more diverse and healthy microbiome. The current study will involve Fecal Microbiota Transplantation (FMT) before the start of the immunotherapy combination, and during the first two cycles of ipilimumab treatment (the more toxic agent) as supportive therapy to prevent toxicity associated with the ipi/nivo combination. The goal of this project is to study the safety of such FMT combination treatment and reduce occurrence of immune-related toxicities in patients, allowing them to continue their cancer treatments in the hopes of a better outcome. The investigators will also be looking at changes in the immune populations, microbiome profile of patients, response to treatment, and patient survival as secondary objectives.

Research Team

Ricardo Fernandes, MD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Saman Maleki, PhD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Eligibility Criteria

This trial is for adults with advanced or metastatic renal cell carcinoma, specifically those at intermediate or poor risk. Participants must be in good physical condition (KPS ≥70%), able to swallow capsules, and have not had certain prior treatments including systemic therapy for RCC. Pregnant individuals, those with immunodeficiency, chronic intestinal diseases, active infections requiring systemic therapy, or a history of serious autoimmune disease are excluded.

Inclusion Criteria

Understand non-infectious risks associated with FMT administration and that the long term data regarding safety risks of FMT are lacking

Able to provide written informed consent

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

I haven't had radiation for bone metastasis in the last 2 weeks or any radiation in the last 4 weeks.

I have not received a live vaccine in the last 4 weeks.

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Fecal Microbiota Transplantation

Participants receive Fecal Microbiota Transplantation before the start of immunotherapy and during the first two cycles of ipilimumab treatment

10 weeks

4 visits (in-person)

Immunotherapy Treatment

Participants receive combination treatment with ipilimumab and nivolumab

28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fecal Microbiota Transplantation

Trial Overview The study tests if Fecal Microbiota Transplantation (FMT) can reduce the side effects of ipilimumab/nivolumab immunotherapy in kidney cancer patients. The goal is to allow patients to tolerate their cancer treatment better by altering gut bacteria before and during the first two cycles of this powerful but potentially toxic drug combination.

Participant Groups

Group I: Fecal Microbiota Transplantation Experimental Treatment 1 Intervention

Fecal microbiota transplantation combined with approved standard of care treatment with nivolumab and ipilimumab.

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Academic Medical Organization of Southwestern Ontario

Collaborator

Trials

17

Recruited

1,600+

Findings from Research

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

A study involving 123 patients who underwent fecal microbiota transplantation (FMT) over a median follow-up of 30.3 months showed that FMT has an excellent long-term safety profile, with new medical conditions being unlikely to be related to the procedure.

In patients with recurrent Clostridioides difficile infection, FMT was associated with a significantly higher survival probability compared to those treated with antibiotics, indicating its efficacy in improving long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry. Yau, YK., Lau, LHS., Lui, RNS., et al.[2023]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

Fecal microbiota transplantation (FMT) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

A kidney transplant recipient successfully treated recurrent urinary tract infections with fecal microbiota transplantation (FMT), remaining symptom-free after the procedure.

The study highlights the need for further research to understand the underlying mechanisms of how FMT works in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. Biehl, LM., Cruz Aguilar, R., Farowski, F., et al.[2019]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

Fecal microbiota transplantation (FMT) is primarily used to treat gastrointestinal diseases caused by harmful microorganisms, but it is also being explored for conditions like metabolic syndrome, diabetes, cancer, and Parkinson's disease.

The review discusses the effects of FMT on weight gain, immune response, and various diseases, while also addressing potential side effects that recipients may experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in disease therapy. Antushevich, H.[2020]

Fecal microbiota transplantation (FMT) is an effective treatment for restoring healthy gut bacteria in patients with disrupted intestinal microbiota, particularly in conditions like Clostridium difficile infection.

The review emphasizes the importance of careful donor selection and proper processing and storage of fecal material to ensure the safety and efficacy of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. Iakupova, AA., Abdulkhakov, SR., Safin, AG., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry. [2023]

4. China pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia-A Literature Review. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in disease therapy. [2020]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. [2022]